Toxicological Sciences 58, 315-323 (2000)
Copyright © 2000 by the Society of Toxicology
Neurotoxicology |
Predicting Exposure Conditions that Facilitate the Potentiation of Noise-Induced Hearing Loss by Carbon Monoxide
Center for Toxicology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190
Hearing loss is the most common occupational disease in the United States, with noise serving as the presumed causative agent in most instances. This investigation characterizes the exposure conditions that facilitate the potentiation of noise-induced hearing loss (NIHL) by carbon monoxide (CO). Auditory function was compared in rats exposed 4 weeks earlier to noise alone, CO alone, combined exposure, and air in the exposure chamber. This interval between exposure and auditory threshold assessment was selected to permit recovery of temporary threshold shifts. The compound action potential (CAP) threshold evoked by pure tone stimuli was used as a measure of auditory sensitivity. The no adverse effect level (NOAEL) with respect to potentiation of NIHL was found to be 300 ppm CO. Potentiation of NIHL by CO increases linearly as CO concentration increases between 500 –1500 ppm. Benchmark dose software (version 1.1B) published by the U.S. EPA National Center for Environmental Assessment was employed to determine a benchmark concentration of CO that produced either a 5-dB potentiation of NIHL or an increase in auditory threshold equivalent to 10% of the effect of noise alone. The lower bound for these benchmark concentrations were 320 and 194 ppm CO, respectively. Unlike CO dose, the relationship between noise severity and potentiation of NIHL by CO shows a nonlinear relationship. The greatest potentiation was observed at moderate noise exposures (100 dB, 2-h, octave band–limited noise, or OBN) that produce limited permanent threshold shifts. Repeated exposures to 95-dB noise for 2-h periods in combination with 1200 ppm CO also yielded potentiation of NIHL, though such effects were not observed following a single combined exposure. These results underscore the potential risk of hearing loss from combined exposure to noise and CO, and the risks associated with repeated exposure.
Key Words: carbon monoxide; ototoxicity; chemical asphyxiants; noise; risk assessment; complex exposures; rat.
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